| Drug | Type of interaction | Effect on theophylline serum concentrations or pharmacologic effect |
| Interferon, human recombinant alpha-A | Decreases theophylline clearance | 100 percent increase |
| Isoproterenol (IV) | Increases theophylline clearance | 20 percent decrease |
| Ketamine | Pharmacologic | May lower theophylline seizure threshold |
| Lithium | Theophylline increases lithium renal clearance | Lithium dose required to achieve a therapeutic serum concentration increased an average of 60 percent |
| Lorazepam | Similar to diazepam | Similar to diazepam |
| Methotrexate (MTX) | Decreases theophylline clearance | 20 percent increase after low-dose MTX, higher dose MTX may have a greater effect |
| Mexiletine | Similar to disulfiram | 80 percent increase |
| Midazolam | Similar to diazepam | Similar to diazepam |
| Moricizine | Increases theophylline clearance | 25 percent decrease |
| Pancuronium | Theophylline may antagonize non-depolarizing neuromuscular blocking effects; possibly due to phosphodiesterase inhibition | Larger dose of pancuronium may be required to achieve neuromuscular blockade |
| Pentoxifylline | Decreases theophylline clearance | 30 percent increase |
| Phenobarbital (PB) | Similar to aminoglutethimide | 25 percent decrease after more than two weeks of concurrent PB |
| Phenytoin | Phenytoin increases theophylline clearance by increasing microsomal enzyme activity | Serum theophylline and phenytoin concentrations decrease about 40 percent |
| Theophylline decreases phenytoin absorption | ||
| Propafenone | Decreases theophylline clearance and pharmacologic interaction | 40 percent increase. Beta-2-blocking effect may decrease efficacy of theophylline |
| Propranolol | Similar to cimetidine and pharmacologic interaction | 100 percent increase. Beta-2-blocking effect may decrease efficacy of theophylline |
| Rifampin | Increases theophylline clearance by increasing cytochrome P450 1A2 and 3A3 activity | 20 to 40 percent decrease |
| Sulfinpyrazone | Increases theophylline clearance by increasing demethylation and hydroxylation. Decreases renal clearance of theophylline | 20 percent decrease |
| Tacrine | Similar to cimetidine, also increases renal clearance of theophylline | 90 percent increase |
| Thiabendazole | Decreases theophylline clearance | 190 percent increase |
| Ticlopidine | Decreases theophylline clearance | 60 percent increase |
| Troleandomycin | Similar to erythromycin | 33 to 100 percent increase depending on troleandomycin dose |
| Verapamil | Similar to disulfiram | 20 percent increase |
| Zafirlukast | Mechanism not studied; theophylline decreases either bioavailability or clearance of zafirlukast. Zafirlukast has no effect on theophylline clearance | Zafirlukast blood levels decrease an average of 40 percent, which is likely to render it ineffective |
| Zileuton | Zileuton inhibits cytochrome P-450 1A2 and, thus, decreases theophylline clearance | 100 percent increase |
